Identification of Regulatory T Cells in Tolerated Allografts

doi:10.1084/jem.20012097

Published online 10 June 2002 doi:10.1084/jem.20012097

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© Rockefeller University Press, 0022-1007/2002/6/1641/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 12, June 17, 2002 1641-1646

Brief Definitive Report

Identification of Regulatory T Cells in Tolerated Allografts

Luis Graca, Stephen P. Cobbold and Herman Waldmann

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

Address correspondence to Luis Graca, Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX1 3RE, UK. Phone: 44-1865-275606; Fax: 44-1865-275501; E-mail: luis.graca{at}pathology.oxford.ac.uk

Induction of transplantation tolerance with certain therapeuticnondepleting monoclonal antibodies can lead to a robust stateof peripheral "dominant" tolerance. Regulatory CD4⁺ T cells,which mediate this form of "dominant" tolerance, can be isolatedfrom spleens of tolerant animals. To determine whether therewere any extra-lymphoid sites that might harbor regulatory Tcells we sought their presence in tolerated skin allograftsand in normal skin. When tolerated skin grafts are retransplantedonto T cell–depleted hosts, graft-infiltrating T cellsexit the graft and recolonize the new host. These colonizingT cells can be shown to contain members with regulatory function,as they can prevent nontolerant lymphocytes from rejecting freshskin allografts, without hindrance of rejection of third partyskin. Our results suggest that T cell suppression of graft rejectionis an active process that operates beyond secondary lymphoidtissue, and involves the persistent presence of regulatory Tcells at the site of the tolerated transplant.

Key Words: adoptive transfer • monoclonal antibodies • skin transplantation • tolerance • anergy

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